But-2-Ene

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform

Toshio Okano - One of the best experts on this subject based on the ideXlab platform.

  • Differential activities of 1α,25-dihydroxy-16-ene-vitamin D3 analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, Mei-ling Siu–caldera, G. Satyanarayana Reddy, Milan R. Uskokovic, Toshio Okano
    Abstract:

    Abstract To clarify physiological role of the carbon 3 (C-3) epimerization of 1α,25(OH)2D3 and biologic significance of a 3-epi metabolite of 1α,25(OH)2D3, we examined biologic activities of the 3-epimers of 1α,25(OH)2D3 and 1α,25(OH)2-16-ene-D3 analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRα heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRα/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1α,25(OH)2D3, 2) 1α,25(OH)2-3-epi-D3, 3) 1α,25(OH)2-16-ene-D3, 4) 1α,25(OH)2-16-ene-3-epi-D3, 5) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-D3, 6) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-3-epi-D3, 7) 1α,25-(OH)2-16-ene-20-epi-23-yne-D3, and 8) 1α,25(OH)2-16-ene-20-epi-23-yne-3-epi-D3. When compared to the 3-natural (β) analogs, the 3-epi (α) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1α,25(OH)2D3 and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (β) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1α,25(OH)2D3 plays an important role to modulate HL-60 cell differentiation and apoptosis.

  • Differential activities of 1alpha,25-dihydroxy-16-ene-vitamin D(3) analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis.
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, G. Satyanarayana Reddy, Milan R. Uskokovic, M L Siu-caldera, Toshio Okano
    Abstract:

    To clarify physiological role of the carbon 3 (C-3) epimerization of 1alpha,25(OH)(2)D(3) and biologic significance of a 3-epi metabolite of 1alpha,25(OH)(2)D(3), we examined biologic activities of the 3-epimers of 1alpha,25(OH)(2)D(3) and 1alpha,25(OH)(2)-16-ene-D(3) analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRalpha heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRalpha/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1alpha,25(OH)(2)D(3), 2) 1alpha,25(OH)(2)-3-epi-D(3), 3) 1alpha,25(OH)(2)-16-ene-D(3), 4) 1alpha,25(OH)(2)-16-ene-3-epi-D(3), 5) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-D(3), 6) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-3-epi-D(3), 7) 1alpha,25-(OH)(2)-16-ene-20-epi-23-yne-D(3), and 8) 1alpha,25(OH)(2)-16-ene-20-epi-23-yne-3-epi-D(3). When compared to the 3-natural (beta) analogs, the 3-epi (alpha) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1alpha,25(OH)(2)D(3) and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (beta) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1alpha,25(OH)(2)D(3) plays an important role to modulate HL-60 cell differentiation and apoptosis.

Milan R. Uskokovic - One of the best experts on this subject based on the ideXlab platform.

  • Differential activities of 1α,25-dihydroxy-16-ene-vitamin D3 analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, Mei-ling Siu–caldera, G. Satyanarayana Reddy, Milan R. Uskokovic, Toshio Okano
    Abstract:

    Abstract To clarify physiological role of the carbon 3 (C-3) epimerization of 1α,25(OH)2D3 and biologic significance of a 3-epi metabolite of 1α,25(OH)2D3, we examined biologic activities of the 3-epimers of 1α,25(OH)2D3 and 1α,25(OH)2-16-ene-D3 analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRα heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRα/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1α,25(OH)2D3, 2) 1α,25(OH)2-3-epi-D3, 3) 1α,25(OH)2-16-ene-D3, 4) 1α,25(OH)2-16-ene-3-epi-D3, 5) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-D3, 6) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-3-epi-D3, 7) 1α,25-(OH)2-16-ene-20-epi-23-yne-D3, and 8) 1α,25(OH)2-16-ene-20-epi-23-yne-3-epi-D3. When compared to the 3-natural (β) analogs, the 3-epi (α) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1α,25(OH)2D3 and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (β) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1α,25(OH)2D3 plays an important role to modulate HL-60 cell differentiation and apoptosis.

  • Differential activities of 1alpha,25-dihydroxy-16-ene-vitamin D(3) analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis.
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, G. Satyanarayana Reddy, Milan R. Uskokovic, M L Siu-caldera, Toshio Okano
    Abstract:

    To clarify physiological role of the carbon 3 (C-3) epimerization of 1alpha,25(OH)(2)D(3) and biologic significance of a 3-epi metabolite of 1alpha,25(OH)(2)D(3), we examined biologic activities of the 3-epimers of 1alpha,25(OH)(2)D(3) and 1alpha,25(OH)(2)-16-ene-D(3) analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRalpha heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRalpha/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1alpha,25(OH)(2)D(3), 2) 1alpha,25(OH)(2)-3-epi-D(3), 3) 1alpha,25(OH)(2)-16-ene-D(3), 4) 1alpha,25(OH)(2)-16-ene-3-epi-D(3), 5) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-D(3), 6) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-3-epi-D(3), 7) 1alpha,25-(OH)(2)-16-ene-20-epi-23-yne-D(3), and 8) 1alpha,25(OH)(2)-16-ene-20-epi-23-yne-3-epi-D(3). When compared to the 3-natural (beta) analogs, the 3-epi (alpha) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1alpha,25(OH)(2)D(3) and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (beta) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1alpha,25(OH)(2)D(3) plays an important role to modulate HL-60 cell differentiation and apoptosis.

  • 1α 25 dihydroxy 24 oxo 16 ene vitamin d3 a metabolite of a synthetic vitamin d3 analog 1α 25 dihydroxy 16 ene vitamin d3 is equipotent to its parent in modulating growth and differentiation of human leukemic cells
    The Journal of Steroid Biochemistry and Molecular Biology, 1996
    Co-Authors: Meiling Siucaldera, Milan R. Uskokovic, Jeffrey Clark, Anabela Santosmoore, Sara Peleg, Yan Yun Liu, Surendra Sharma, Satyanarayana G Reddy
    Abstract:

    Abstract 1α,25(OH)2-16-ene-D3, a synthetic analog of the steroid hormone, 1α,25(OH)2D3, has great potential to become a drug in the treatment of leukemia and other proliferative disorders, because of its minimal in vivo calcemic activity associated with a potent inhibitory effect on cell growth. However, at present, the mechanisms through which 1α,25(OH)2-16-ene-D3 expresses its biological activities are still not completely understood. Our previous in vitro study in a perfused rat kidney indicated for the first time that 1α,25(OH)2-16-ene-D3 and 1α,25(OH)2D3 are metabolized differently. 1α,25(OH)2-24-oxo-16-ene-D3, an intermediary metabolite of 1α,25(OH)2-16-ene-D3 formed through the C-24 oxidation pathway, accumulated significantly in the perfusate when compared to 1α,25(OH)2-24-oxo-D3, the corresponding intermediary metabolite of 1α,25(OH)2D3. In a subsequent in vivo study, we also reported that 1α,25(OH)2-24-oxo-16-ene-D3 exerted immunosuppressive activity equal to its parent, without causing significant hypercalcemia. In order to establish further the critical role of 1α,25(OH)2-24-oxo-16-ene-D3, in generating some of the key biological activities ascribed to its parent, we performed the present in vitro study using a human myeloid leukemic cell line (RWLeu-4) as a model. Comparative target tissue metabolism studies indicated that 1α,25(OH)2-16-ene-D3 and 1α,25(OH)2D3 are metabolized differently in RWLeu-4 cells, and the differences were similar to the ones we previously observed in the rat kidney. The significant finding was the accumulation of 1α,25(OH)2-24-oxo-16-ene-D3 in RWLeu-4 cells because of its resistance to further metabolism. Biological activity studies indicated that both 1α,25(OH)2-16-ene-D3 and its 24-oxo metabolite produced growth inhibition and promoted differentiation of RWLeu-4 cells to the same extent, and these activities were several fold higher than those exerted by 1α,25(OH)2D3. In addition, the genomic action of each vitamin D compound was assessed in a rat osteosarcoma cell line (ROS 17 2.8 ) by measuring its ability to transactivate a gene construct containing the vitamin D response element of the osteocalcin gene linked to the growth hormone reporter gene. In these studies, both 1α,25(OH)2-16-ene-D3 and its 24-oxo metabolite exerted similar but potent transactivation activity which was several fold greater than that exerted by 1α,25(OH)2D3 itself. In summary, our results indicate that the production and slow clearance of the bioactive intermediary metabolite, 1α,25(OH)2-24-oxo-16-ene-D3, in RWLeu-4 cells contributes significantly to the final expression of the enhanced biological activities ascribed to its parent analog, 1α,25(OH)2-16-ene-D3.

Kimie Nakagawa - One of the best experts on this subject based on the ideXlab platform.

  • Differential activities of 1α,25-dihydroxy-16-ene-vitamin D3 analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, Mei-ling Siu–caldera, G. Satyanarayana Reddy, Milan R. Uskokovic, Toshio Okano
    Abstract:

    Abstract To clarify physiological role of the carbon 3 (C-3) epimerization of 1α,25(OH)2D3 and biologic significance of a 3-epi metabolite of 1α,25(OH)2D3, we examined biologic activities of the 3-epimers of 1α,25(OH)2D3 and 1α,25(OH)2-16-ene-D3 analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRα heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRα/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1α,25(OH)2D3, 2) 1α,25(OH)2-3-epi-D3, 3) 1α,25(OH)2-16-ene-D3, 4) 1α,25(OH)2-16-ene-3-epi-D3, 5) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-D3, 6) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-3-epi-D3, 7) 1α,25-(OH)2-16-ene-20-epi-23-yne-D3, and 8) 1α,25(OH)2-16-ene-20-epi-23-yne-3-epi-D3. When compared to the 3-natural (β) analogs, the 3-epi (α) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1α,25(OH)2D3 and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (β) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1α,25(OH)2D3 plays an important role to modulate HL-60 cell differentiation and apoptosis.

  • Differential activities of 1alpha,25-dihydroxy-16-ene-vitamin D(3) analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis.
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, G. Satyanarayana Reddy, Milan R. Uskokovic, M L Siu-caldera, Toshio Okano
    Abstract:

    To clarify physiological role of the carbon 3 (C-3) epimerization of 1alpha,25(OH)(2)D(3) and biologic significance of a 3-epi metabolite of 1alpha,25(OH)(2)D(3), we examined biologic activities of the 3-epimers of 1alpha,25(OH)(2)D(3) and 1alpha,25(OH)(2)-16-ene-D(3) analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRalpha heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRalpha/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1alpha,25(OH)(2)D(3), 2) 1alpha,25(OH)(2)-3-epi-D(3), 3) 1alpha,25(OH)(2)-16-ene-D(3), 4) 1alpha,25(OH)(2)-16-ene-3-epi-D(3), 5) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-D(3), 6) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-3-epi-D(3), 7) 1alpha,25-(OH)(2)-16-ene-20-epi-23-yne-D(3), and 8) 1alpha,25(OH)(2)-16-ene-20-epi-23-yne-3-epi-D(3). When compared to the 3-natural (beta) analogs, the 3-epi (alpha) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1alpha,25(OH)(2)D(3) and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (beta) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1alpha,25(OH)(2)D(3) plays an important role to modulate HL-60 cell differentiation and apoptosis.

Yoshiko Sowa - One of the best experts on this subject based on the ideXlab platform.

  • Differential activities of 1α,25-dihydroxy-16-ene-vitamin D3 analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, Mei-ling Siu–caldera, G. Satyanarayana Reddy, Milan R. Uskokovic, Toshio Okano
    Abstract:

    Abstract To clarify physiological role of the carbon 3 (C-3) epimerization of 1α,25(OH)2D3 and biologic significance of a 3-epi metabolite of 1α,25(OH)2D3, we examined biologic activities of the 3-epimers of 1α,25(OH)2D3 and 1α,25(OH)2-16-ene-D3 analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRα heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRα/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1α,25(OH)2D3, 2) 1α,25(OH)2-3-epi-D3, 3) 1α,25(OH)2-16-ene-D3, 4) 1α,25(OH)2-16-ene-3-epi-D3, 5) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-D3, 6) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-3-epi-D3, 7) 1α,25-(OH)2-16-ene-20-epi-23-yne-D3, and 8) 1α,25(OH)2-16-ene-20-epi-23-yne-3-epi-D3. When compared to the 3-natural (β) analogs, the 3-epi (α) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1α,25(OH)2D3 and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (β) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1α,25(OH)2D3 plays an important role to modulate HL-60 cell differentiation and apoptosis.

  • Differential activities of 1alpha,25-dihydroxy-16-ene-vitamin D(3) analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis.
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, G. Satyanarayana Reddy, Milan R. Uskokovic, M L Siu-caldera, Toshio Okano
    Abstract:

    To clarify physiological role of the carbon 3 (C-3) epimerization of 1alpha,25(OH)(2)D(3) and biologic significance of a 3-epi metabolite of 1alpha,25(OH)(2)D(3), we examined biologic activities of the 3-epimers of 1alpha,25(OH)(2)D(3) and 1alpha,25(OH)(2)-16-ene-D(3) analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRalpha heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRalpha/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1alpha,25(OH)(2)D(3), 2) 1alpha,25(OH)(2)-3-epi-D(3), 3) 1alpha,25(OH)(2)-16-ene-D(3), 4) 1alpha,25(OH)(2)-16-ene-3-epi-D(3), 5) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-D(3), 6) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-3-epi-D(3), 7) 1alpha,25-(OH)(2)-16-ene-20-epi-23-yne-D(3), and 8) 1alpha,25(OH)(2)-16-ene-20-epi-23-yne-3-epi-D(3). When compared to the 3-natural (beta) analogs, the 3-epi (alpha) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1alpha,25(OH)(2)D(3) and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (beta) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1alpha,25(OH)(2)D(3) plays an important role to modulate HL-60 cell differentiation and apoptosis.

Keiichi Ozono - One of the best experts on this subject based on the ideXlab platform.

  • Differential activities of 1α,25-dihydroxy-16-ene-vitamin D3 analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, Mei-ling Siu–caldera, G. Satyanarayana Reddy, Milan R. Uskokovic, Toshio Okano
    Abstract:

    Abstract To clarify physiological role of the carbon 3 (C-3) epimerization of 1α,25(OH)2D3 and biologic significance of a 3-epi metabolite of 1α,25(OH)2D3, we examined biologic activities of the 3-epimers of 1α,25(OH)2D3 and 1α,25(OH)2-16-ene-D3 analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRα heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRα/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1α,25(OH)2D3, 2) 1α,25(OH)2-3-epi-D3, 3) 1α,25(OH)2-16-ene-D3, 4) 1α,25(OH)2-16-ene-3-epi-D3, 5) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-D3, 6) 1α,25(OH)2-16-ene-23-yne-hexafluoro(F6)-3-epi-D3, 7) 1α,25-(OH)2-16-ene-20-epi-23-yne-D3, and 8) 1α,25(OH)2-16-ene-20-epi-23-yne-3-epi-D3. When compared to the 3-natural (β) analogs, the 3-epi (α) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1α,25(OH)2D3 and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (β) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1α,25(OH)2D3 plays an important role to modulate HL-60 cell differentiation and apoptosis.

  • Differential activities of 1alpha,25-dihydroxy-16-ene-vitamin D(3) analogs and their 3-epimers on human promyelocytic leukemia (HL-60) cell differentiation and apoptosis.
    Steroids, 2001
    Co-Authors: Kimie Nakagawa, Yoshiko Sowa, Mayuko Kurobe, Keiichi Ozono, G. Satyanarayana Reddy, Milan R. Uskokovic, M L Siu-caldera, Toshio Okano
    Abstract:

    To clarify physiological role of the carbon 3 (C-3) epimerization of 1alpha,25(OH)(2)D(3) and biologic significance of a 3-epi metabolite of 1alpha,25(OH)(2)D(3), we examined biologic activities of the 3-epimers of 1alpha,25(OH)(2)D(3) and 1alpha,25(OH)(2)-16-ene-D(3) analogs in terms of modulation of cell cycle phase distribution and cell-surface CD11b antigen expression of HL-60 cells, transactivation of vitamin D target genes in transfected cells, stimulation of VDR/RXRalpha heterodimer formation in a rabbit reticulocyte lysates transcription/translation system, stimulation of VDR/RXRalpha/VDRE complex formation, and induction of HL-60 cell apoptosis. The analogs tested here were 1) 1alpha,25(OH)(2)D(3), 2) 1alpha,25(OH)(2)-3-epi-D(3), 3) 1alpha,25(OH)(2)-16-ene-D(3), 4) 1alpha,25(OH)(2)-16-ene-3-epi-D(3), 5) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-D(3), 6) 1alpha,25(OH)(2)-16-ene-23-yne-hexafluoro(F(6))-3-epi-D(3), 7) 1alpha,25-(OH)(2)-16-ene-20-epi-23-yne-D(3), and 8) 1alpha,25(OH)(2)-16-ene-20-epi-23-yne-3-epi-D(3). When compared to the 3-natural (beta) analogs, the 3-epi (alpha) analogs were biologically significantly less active. The findings support the hypothesis that the C-3 epimerization is an inactivation pathway of 1alpha,25(OH)(2)D(3) and its analogs in vitamin D target tissues. We also found that the 3-epi analogs, but not the 3-natural (beta) analogs, were the potent inducers of apoptosis of HL-60 cells. These results suggest that the analogs could be divided into two groups, in which the 3-epi analogs were the potent inducers of apoptosis of HL-60 cells, and the 3-natural analogs were the potent modulators of HL-60 cell growth and differentiation. This is the first report demonstrating that the 3-epimerization of the hydroxyl group at C-3 of the A-ring of 1alpha,25(OH)(2)D(3) plays an important role to modulate HL-60 cell differentiation and apoptosis.

Related terms

But-2-Ene - 15 days free trial to Access Experts & Abstracts